Parkinson's disease (PD) affects an estimated one million persons in the United States and results in significant disability as the disease progresses, in many cases making daily activities difficult to complete. This disability leads to deterioration in the quality of life of both persons with PD and their caregivers. It also significantly increases healthcare costs and usage including hospitalizations and nursing home placement. One of the largest unmet needs in PD research is the identification of treatments that could be neuroprotective or slow the progression of the disease. The NET-PD program was established to address this issue by forming a network of clinical centers throughout North America with designated coordinating and statistical centers to identify and examine potential neuroprotective therapies. As part of this initiative 2 futility trials examining creatine, minocycline, co-enzyme Q10 and GPI-1485 were conducted as a unique approach for PD studies, to quickly identify potentially neuroprotective therapies. These studies suggested that creatine may have potential as a neuroprotective therapy for PD while the other therapies were found to be futile. This led to a large simple study of creatine (LS-1) which is a Phase III, randomized, double-blind, placebo-controlled, multi-center trial. The University of Kansas Medical Center enrolled subjects in both futility trials and is currently participating in the LS-1 study (31 subjects enrolled) as well as an additional trial, FS-ZONE, to examine the potential neuroprotective properties of pioglitazone. The specific aims of the current proposal are to complete ail follow-up evaluations such that the last subject enrolled in LS-1 has at least 5 years of follow-up. The study will allow for the examination of the long-term safety and efficacy of creatine as well as an examination of multiple data points to determine if there is a slowing of disease progression. The focus of the University of Kansas will be to complete all required study visits and assessments and to make sure that all remaining subjects (28) continue their participation in the study until its completion.